Investigation of the synergistic effect of ceftazidime-avibactam and aztreonam combination on carbapenem-resistant Klebsiella pneumoniae isolates with 3 different methods.

Abstract

Treatment options are limited for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates due to the production of metallo-β-lactamase (MBL). The ceftazidime-avibactam (CZA)/ aztreonam (ATM) combination represents a new therapeutic approach in MBL-positive isolates. Our study aims to determine distribution of carbapenemase genes in CRKP isolates and to investigate the in vitro synergistic effect of the CZA/ATM combination.Our study included 48 CRKP strains isolated from various clinical samples. Identification was performed using MALDI-TOF MS (bioMérieux, France), and susceptibility was tested with Vitek-2 (bioMérieux). The susceptibility to CZA and ATM was determined using CZA 30/20 µg and ATM 30 µg (Oxoid™,UK) disks. Carbapenemase genes VIM, NDM, IMP, KPC, OXA-23, OXA-58, OXA-48, and OXA-51 were investigated in only 44 isolates using the Bio-Speedy Carbapenem resistance qPCR (Bioexen, Turkiye) kit. Synergy testing was evaluated with double disk diffusion, gradient strip (bioMérieux)/disk diffusion, and broth disk elution methods.Out of 48 carbapenem-resistant isolates, 40 (83.3%) isolates showed resistance to CZA and 46 (95.8%) to aztreonam. Synergy was detected with all three methods in all isolates identified as resistant to CZA, CZA-sensitive isolates were not included in this evaluation. The most frequently detected carbapenemase genes were NDM+OXA-48, found in 28 (63.6%) of the isolates.Although the NDM+OXA-48 coexistence predominates in our center, in vitro synergy between CZA and ATM was detected in all of CZA-resistant isolates. Performing the CZA+ATM synergy test and reporting the result is crucial for choosing appropriate treatment in CRKP infection.